Comparative Effectiveness of Intensity-Modulated Proton Therapy Versus Intensity-Modulated Radiotherapy for Patients With Inoperable Esophageal Squamous Cell Carcinoma Undergoing Curative-Intent Concurrent Chemoradiotherapy

Abstract

IntroductionThis study compared outcomes in patients with inoperable esophageal squamous cell carcinoma (ESCC) undergoing curative-intent concurrent chemoradiotherapy (CCRT) with intensity-modulated radiotherapy (IMRT) versus intensity-modulated proton therapy (IMPT). MethodsThe study encompassed a retrospective cohort analysis of patients with inoperable ESCC who underwent curative-intent CCRT from January 1, 2015, to December 31, 2020, with data sourced from the Taiwan Cancer Registry Database. In this study, both IMRT and IMPT delivered a total equivalent effective dose of approximately 5040 cGy in 28 fractions, accompanied by platinum-based chemotherapy administered as per established protocols. Multivariate Cox regression analyses were performed to assess oncologic outcomes, and statistical analyses were conducted, including inverse probability of treatment-weighted and Fine and Gray method for competing risks. ResultsThe observed risks of ESCC-specific and all-cause mortality were lower in patients treated with IMPT compared with those treated with IMRT, with adjusted hazard ratios (aHRs) of 0.62 (95% confidence interval [CI]: 0.58–0.70) and 0.72 (95% CI: 0.66–0.80), respectively. IMPT also reduced grade 2 radiation-induced side effects, such as pneumonitis, fatigue, and major adverse cardiovascular events, with aHRs (95% CI) of 0.76 (0.66–0.82), 0.10 (0.07–0.14), and 0.70 (0.67–0.73), respectively. However, IMPT was associated with an increased risk of grade 2 radiation dermatitis, with aHR (95% CI) of 1.48 (1.36–1.60). No substantial differences were found in the incidence of radiation esophagitis between IMPT and IMRT when adjusting for covariates. ConclusionIMPT seems to be associated with superiority over IMRT in managing patients with inoperable ESCC undergoing curative-intent CCRT, suggesting improved survival outcomes and reduced toxicity. These findings have significant implications for the treatment of ESCC, particularly when surgery is not an option.